ABSTRACT This application requests funds for a light sheet (LS) microscope to be housed in Cornell?s Biotechnology Resource Center (BRC)-Imaging core facility, with data handling and storage infrastructure to be supported by Cornell?s BRC Bio-IT and BioComputing facilities. The main purpose of the instrument will be to provide fast, flexible, three-dimensional fluorescence imaging of cleared whole organs, for fundamental research into developmental biology and neuroscience. Currently, researchers on the Ithaca campus use confocal microscopy to image cleared tissue samples, which can be so expensive and time-consuming that reasonable numbers of samples are simply not feasible. LS microscopy has become the method of choice for imaging transparent or chemically cleared samples rapidly and with minimal photobleaching, reducing the time and costs associated with specimen imaging 100-fold. LS microscopy thus enables a major advancement in the scale and nature of experiments that can be undertaken. It also enables imaging of tissue structures with measurements that are not stretched in the axial direction, giving data sets that are higher quality than can be achieved with confocal microscopy. This microscope will be integrated into the educational and IT infrastructure of the imaging core facility. BRC staff will oversee shared access and maintenance so that it will sustain optimized imaging throughout its lifetime.